Approaches to Therapeutic Gene Editing in Alpha-1 Antitrypsin Deficiency.

Abstract

Five distinct gene therapy approaches have been developed for treating AATD. These approaches include knockout of the mutant (PiZ) allele by introduction of double-strand breaks (DSBs) and subsequent creation of insertions and deletions (indels) by DSB repair, homology-directed repair (HDR) targeted to the mutation site, base editing, prime editing, and alternatively targeted knock-in techniques. Each approach will be discussed and a brief summary of a standard CRISPR-Cas9 targeting method will be presented.